Identification of Fluorescent Small Molecule Compounds for Synaptic Labeling by Image-Based, High-Content Screening,ACS Chemical Neuroscience

当前位置： X-MOL 学术 › ACS Chem. Neurosci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Identification of Fluorescent Small Molecule Compounds for Synaptic Labeling by Image-Based, High-Content Screening
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2017-12-07 00:00:00 , DOI: 10.1021/acschemneuro.7b00263
Matthew Dunn _{1,

2,

3} , Umed Boltaev _{1,

2} , Anne Beskow ₄ , Sergey Pampou ₅ , Ronald Realubit ₅ , Torcato Meira _{6,

7} , João Vaz Silva _{4,

7} , Rose Reeb ₄ , Charles Karan ₅ , Steffen Jockusch ₁ , David Sulzer ₃ , Young Tae Chang ₈ , Dalibor Sames _{1,

2} , Clarissa L Waites _{4,

6}

Affiliation

Few tools are available for noninvasive imaging of synapses in the living mammalian brain. Current paradigms require the use of genetically modified mice or viral delivery of genetic material to the brain. To develop an alternative chemical approach, utilizing the recognition of synaptic components by organic small molecules, we designed an imaging-based, high-content screen in cultured cortical neurons to identify molecules based on their colocalization with fluorescently tagged synaptic proteins. We used this approach to screen a library of ∼7000 novel fluorescent dyes, and identified a series of compounds in the xanthone family that exhibited consistent synaptic labeling. Follow-up studies with one of these compounds, CX-G3, demonstrated its ability to label acidic organelles and in particular synaptic vesicles at glutamatergic synapses in cultured neurons and murine brain tissue, indicating the potential of this screening approach to identify promising lead compounds for use as synaptic markers, sensors, and targeting devices.

中文翻译：

通过基于图像的高内涵筛选鉴定用于突触标记的荧光小分子化合物

很少有工具可用于对活的哺乳动物大脑中的突触进行无创成像。当前的范例需要使用转基因小鼠或将遗传物质病毒传递到大脑。为了开发一种替代化学方法，利用有机小分子对突触成分的识别，我们在培养的皮层神经元中设计了一种基于成像的高内涵筛选，以根据分子与荧光标记的突触蛋白的共定位来识别分子。我们使用这种方法筛选了一个包含约 7000 种新型荧光染料的文库，并鉴定了一系列具有一致突触标记的呫吨酮家族化合物。使用其中一种化合物 CX-G3 进行后续研究，

更新日期：2017-12-07

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11